Every year, 470,000 cases of cervical cancer are diagnosed. Essentially 100% of cervical cancers contain HPV of the high-risk type (HPV 16 or 18), persistent infection of the cervix with these viruses is considered to be the necessary cause of the disease (90% of other ano-genital cancers also contain HPV). Oral cancer, penile cancer and some neck cancer might be related to HPV infection as well. There are no good therapies when metastasis of HPV induced cancers such as cervical cancer occurs and thus effective new therapies are needed urgently.
Prophylactic vaccines for HPV infection are already approved by the FDA. Gardasil, a virus like particle that targets the L1 protein of HPV types 6, 11, 16 and 18 protects women from infection by HPV close to 100%. This type of vaccine mainly induces a humeral immune response generating antibodies that can neutralize the virus. Gardasil is thus an effective vaccine for preventing HPV infection. However, this kind of vaccine is ineffective for treating HPV+ cancers since both CD4+ and CD8+ T cell immunity must be induced in order to eradicate the HPV+ cancers.
Accumulating data indicate that immunotherapy for cervical cancer and other HPV+ cancers holds promise. The expression of the HPV E6 and E7 genes is found in most cervical cancers as well as other HPV+ cancers, indicating that the HPV oncogenic proteins, E6 and E7, are critical for the induction and maintenance of cellular transformation. The specific expression of these genes in the majority of the HPV+ carcinomas suggests that they are good targets for immunotherapy.
There are several types of therapeutic vaccines being studied currently. 1) Viral vector-based DNA vaccine such as recombinant adenovirus that contains E6 and/or E7 genes. The advantage of this vaccine is that it is a strong immunogen. Disadvantages include safety and cost. 2) Plasmid-based DNA vaccine. The advantage is that these are generally considered safe and economical to produce but so far have proven to be only weakly immunogenic with a low in vivo transfection rate. 3) Peptide vaccine. The advantages are that it is very safe and economical but peptides are generally only weakly immunogenic and HLA-restricted. 4) Protein vaccination. The big advantage here is safety: however, they do not induce good cellular immunity. 5) Dendritic cell (DC)-based vaccine. Autologous DCs pulsed with E7 or E6 proteins are very immunogenic. The disadvantage is the high cost and the labor-intensive methods required for each vaccination.
Thus, an efficient yet safe immunotherapy is needed for treating or preventing HPV+ tumors.